2. series of 130 treated children followed-up 12 years in France,
ocular involvement was found in 30%,14
and in a third series
of French adults (median age = 22 years) who had congenital
toxoplasmosis that was treated pre- and post-natally, 59% had
ocular lesions but only 13% had reduced vision.15
A compar-
ison of cohorts of children with congenital toxoplasmosis in
Brazil with those in Europe found that T. gondii causes more
severe ocular disease in congenitally infected children in
Brazil.9
The authors suggested that the increased frequency
and severity of ocular disease in Brazil compared with that in
Europe may be caused by more virulent type 1 and atypical
strains found there.9
In general, infants born to women who
were infected with T. gondii more than a few weeks before
conception are not at risk for congenital infection, although
congenital infection from women with chronic T. gondii infec-
tion has occurred with reactivation in immunosuppression or
with infection by atypical genotypes.7
Although T. gondii infection appears to be lifelong, for
most healthy persons infected outside of infancy it has long
been believed that further clinical manifestations after acute
infection are rare. However, studies have now revealed asso-
ciations between T. gondii antibody seropositivity (indicating
infection) and the presence of various psychiatric disorders
in humans (e.g., schizophrenia,16
bipolar illness,17
suicide
attempts,18
episodes of self-directed violence,19
and memory
impairment in elderly persons20
). Although these results
are intriguing and potentially signal a new and compelling
reason to redouble efforts to prevent toxoplasmosis, addi-
tional studies are needed to fully elucidate the relationship
between T. gondii infection and mental illness, and how the
strain and stage of T. gondii (oocyst versus tissue cyst) affects
this relationship.21
DIAGNOSIS AND TREATMENT
Toxoplasma gondii infection can be diagnosed by testing
for antibodies against Toxoplasma, as well as by direct test-
ing or visualization of the parasite in body tissues or fluids.
Basic antibody tests (e.g., IgG and IgM) are available com-
mercially. Detection of IgG against Toxoplasma indicates
previous exposure, but does not indicate when infection
occurred. Detection of IgM against Toxoplasma is sugges-
tive of acute infection, but IgM can persist for months or
even years after infection and false-positive IgM test results
can occur in persons who are chronically infected or not
infected with T. gondii.22
Therefore, when clinical action
depends on test results, IgM test results should be verified
at a reference laboratory, especially for pregnant women
and newborns.23
Antibody avidity testing can been used to
help distinguish between recent and distant infection,24
an
important consideration for pregnant women when IgM is
detected and the risk for congenital toxoplasmosis is being
assessed. Avidity testing is available in many countries
including the United States.25
Treatment recommendations vary with the type and sever-
ity of infection. Mild disease in adults with normally func-
tioning immune systems rarely requires treatment, whereas
severe disease, including disease in immunosuppressed per-
sons, requires treatment with a combination of anti-parasitic
medications (e.g., pyrimethamine and sulfadiazine).26,27
Clini-
cal management of pregnant women and infants with congeni-
tal infection is complex and consultation with a specialist
is advised.28
PUBLIC HEALTH SIGNIFICANCE
OF TOXOPLASMOSIS IN THE UNITED STATES
Toxoplasmosis is responsible for considerable morbidity
and mortality in the United States. Serologic evidence of
infection is more frequently seen in black and Hispanic per-
sons, and among persons who are foreign-born, have low edu-
cational levels or socioeconomic status, or have occupations
involving exposure to soil.29,30
Serologic evidence of Toxocara
(dog or cat roundworm) infection, which is soil-borne, is more
commonly seen among those with T. gondii infection, suggest-
ing common risk factors for acquiring the two infections.31
In the United States, studies examining data from the
mid to late 2000s estimated toxoplasmosis to be the second
leading cause of deaths attributable to foodborne illness
(an estimated 327 deaths), the fourth leading cause of hos-
pitalizations attributable to foodborne illness (an estimated
4,428 hospitalizations), and a leading contributor to loss of
quality-adjusted life years.32,33
Toxoplasma gondii infects
an estimated 1.1 million persons each year in the United
States.34
Chorioretinitis caused by infection with T. gondii
develops in an estimated 21,000 persons each year, and symp-
tomatic chorioretinitis, leading to vision loss, develops in more
than 4,800 of these persons.34
Because symptoms in the eye
recur over time and new lesions commonly develop, these
calculations are likely to be minimum estimations of the inci-
dence of symptomatic ocular toxoplasmosis. Ocular toxoplas-
mosis creates a significant burden on the healthcare system,
with an estimated 250,000 visits to ophthalmologists for active
or chronic disease over a two-year period.35
Serologic surveys over past decades indicate that rates of
infection with T. gondii have decreased in the United States.
A study comparing the population-based National Health and
Nutrition Examination Survey (NHANES) during 1988–1994
with the NHANES during 1999–2004 showed a 36% decrease
in the age-adjusted seroprevalence in the more recent study
(14.1% to 9.0% in persons 12–49 years of age).30
Preliminary
results from the NHANES 2009–2010 show further decreases
(Jones J, unpublished data). Because in the older study
(NHANES 1988–1994) all persons ³ 12 years of age were
tested, an estimate could be made for the overall population
in this age range. The age-adjusted T. gondii antibody sero-
prevalence was 22.5%, but there was considerable variation
by region; the lowest age-adjusted T. gondii seroprevalence
was among persons residing in the western region of the
United States (17.5%) and highest in the North-
east (29.2%).29
An estimated 400–4,000 infants are born with congenital
toxoplasmosis each year in the United States.36–38
Overall,
approximately 30% of women who acquire infection during
pregnancy transmit the infection to the fetus; the risk of
transmission from mother to child is lowest when infection
occurs during the first trimester (10–15%) and higher as
pregnancy progresses to the third trimester (60–90%).39
However, injury to the fetus is usually greatest when acute
infection occurs early in pregnancy,39
although some atypical
genotypes can cause severe congenital toxoplasmosis in the
third trimester.7
NEGLECTED PARASITIC INFECTIONS: TOXOPLASMOSIS 795
3. Estimates of the incidence of congenital infections vary in
the United States. The most recently published population-
based estimate is derived from the New England Newborn
Screening program in the late 1980s and early 1990s,38,40
a region shown to have the highest prevalence of T. gondii
infection in the United States.29
Analysis of newborn IgM
blood spot screening tests in Massachusetts and New
Hampshire yielded an estimate of 1 case per 12,212 live
births.40
More recent data from the New England Newborn
Screening Program showed that congenital toxoplasmosis
rates during 2000–2010 ranged from approximately 1.3 to
6.8 per 100,000 live births (Eaton R, unpublished data).
Newborn screening filter paper blood spot IgM test sensitiv-
ity is low (approximately 50–75%).41–43
In addition, because
false-positive IgM test results also occur, serum samples from
the mother and infant must be followed-up to verify true
positive test results.40
Older local studies in the United States
found congenital toxoplasmosis rates of approximately 1 per
1,000 newborns.44,45
Similar to seroprevalence estimates
among adults, rates of congenital infection are likely to vary
by region of the United States.
PREVENTION STRATEGIES
The devastating impact of congenital infection has led to
great interest in reducing risk through screening. In one eco-
nomic analysis, an approach comprised of monthly prenatal
T. gondii screening and treatment of women infected in preg-
nancy coupled with one year of treatment of infected new-
borns with pyrimethamine and sulfonamides was estimated
to be cost saving if the rate of congenital infection was
greater than 1 per 10,000 live births.46
However, the cost
savings were based on an ideal program with all prenatal
visits conducted on time, all tests validated at a highly
expert reference laboratory, and when required, treatment
given soon after maternal seroconversion. The efficacy of
treatment of pregnant women and infants has not been
determined by well-controlled randomized trials, either for
the ability to prevent congenital infection or reduce sequlae
in infected infants. Treatment is thought to be most effec-
tive if given within days to weeks of seroconversion in preg-
nant women. Even in France, where routine screening has
been recommended for decades, a study found late initial
testing and poor compliance with recommended screening
intervals (the first test was performed later than the recom-
mended first 12 weeks of pregnancy in 25% of women, and
only 40% of women had the recommended number of
screening tests in pregnancy).47
In Austria, where prenatal
screening every trimester has been recommended and con-
ducted for three decades, only 30% of seronegative women
were found to be tested at least three times during their
pregnancies.48
These findings imply that in a real-world
setting it can be challenging to screen and treat newly sero-
converted pregnant women soon after infection. Neverthe-
less, the societal and economic costs of care for developmental
disabilities such as congenital toxoplasmosis, estimated to
be from approximately 500,000 to 3.3 million U.S. dollars
per case according to the severity,46
are considerable for
symptomatic cases.
Although there has been some enthusiasm within the
medical community for prenatal or neonatal screening
programs, others, including the United Kingdom National
Screening Committee, have argued that there is currently no
evidence from randomized placebo-controlled trials demon-
strating efficacy for screening and treatment of congenital
toxoplasmosis.49–51
In recent years, prenatal or neonatal toxo-
plasmosis screening has been evaluated but not adopted in
numerous countries in Europe, including the United Kingdom,
Switzerland, and Denmark50–53
; and in Canada and Israel.54,55
Screening in these countries was not adopted because of a
low incidence of T. gondii infection (similar to that of the
United States), concerns about the lack of well-controlled
studies documenting benefit, and concerns about potential
costs and harms of the programs outweighing benefits in a
practical setting. In addition, the American College of
Obstetricians and Gynecologists did not recommend univer-
sal screening of pregnant women for T. gondii infection in
their practice guidelines.56
Studies and systematic reviews
have yielded conflicting results on the benefits of prenatal
screening and treatment of congenital toxoplasmosis.57–66
There is a need for well controlled studies to help determine
the effectiveness these interventions.
Preventing infection of pregnant women through educa-
tion is another potentially beneficial strategy. A study of
pregnant women in the United States found that they often
lack knowledge about how to prevent T. gondii infection,
especially the risks associated with eating or handling raw
or undercooked meat.67
Although numerous studies have
provided some evidence that education of pregnant women
may be beneficial,68–72
one review of toxoplasmosis-related
health education called for more rigorously designed research
on prevention of toxoplasmosis through education, and
questioned the validity of results from published studies.73
In addition, a recent Cochrane systematic review found very
little rigorous scientific evidence that prenatal education is
effective in reducing congenital toxoplasmosis and called for
randomized controlled trials to confirm the potential benefits
and quantify the impact of educational interventions.74
Vaccination of cats for toxoplasmosis has also been pro-
posed as a control method and an oral live vaccine prevented
cats from shedding oocysts in clinical trials.75
However, the
commercial production of toxoplasmosis vaccine for cats
was discontinued because of its high cost, the need to keep
the vaccine frozen, its short shelf life, and lack of interest
among cat owners.1
A live toxoplasmosis vaccine for sheep
that produces protective immunity for 18 months is avail-
able in some countries (but not in the United States) to
reduce loss of lambs.76
Vaccination with killed T. gondii
preparations has been unsuccessful. For humans, develop-
ment of a live mutant or avirulent strain vaccine has not
been pursued because these strains may pose a risk to the
fetus and there is insufficient data on the risk of reversion
to T. gondii strains that could cause disease, particularly in
immunosuppressed persons.
GAPS IN CURRENT KNOWLEDGE
AND PROGRAMATIC INTERVENTIONS
Despite limited data on the incidence and prevalence of
infection and illness caused by T. gondii, toxoplasmosis is
clearly an important public health problem in the United
States and globally. Much remains to be learned about toxo-
plasmosis to improve our knowledge of the disease, as well as
to decrease infection rates through prevention and treatment.
796 JONES AND OTHERS
4. Further insight into the number of children infected by
mother-to-child transmission could be gained by conducting
a pilot prenatal screening and treatment program with active
surveillance for congenital toxoplasmosis. However, the ben-
efits of treatment remain uncertain and treatment trials with
placebo treatment groups might be problematic from an
ethical standpoint. In addition, because the congenital toxo-
plasmosis rate is low in the United States, appropriately
controlled studies of treatment efficacy would require mil-
lions of study participants and be extremely expensive.
Given these limitations, a monitored pilot evaluation of pre-
natal screening and treatment in a high-risk country or geo-
graphic region may be the best practical option, even if only
a subset of the population undergoing prenatal screening is
monitored for outcomes (e.g., randomly selected healthcare
facilities, or sentinel sites).
There are numerous potential T. gondii maternal screening
program pitfalls that include: lack of confirmation of positive
screening test results before taking clinical actions, such as
amniocentesis to assess fetal infection or implementing
treatment; risk of amniocentesis to verify fetal infection;77,78
and late initial testing and poor compliance with screening
intervals that lead to delayed initiation of therapy, as has been
a problem in France and Austria.47,48,79
Because routine
prenatal T. gondii infection screening would be new in low-
incidence countries such as the United States, and the practi-
calities of its implementation in such countries are unknown,
assessments of such screening and treatment programs should
include 1) the proportion of T. gondii testing in pregnancy
performed at correct intervals, and 2) the appropriate use of
reference laboratories to validate test results, 3) evaluation of
elective pregnancy terminations in women who show positive
test results but who have not had their tests results confirmed,
4) the outcome and side effects of amniocentesis used to
verify fetal infection, 5) the side effects of medications used
in pregnant women and infants, 6) the time after maternal
seroconversion that treatment is initiated, 7) the regimen used
for treatment, 8) patient compliance with the treatment,
9) the outcome in infants, and 10) the costs and benefits. In
the United States, if large numbers of tests were performed for
screening, it is not certain that confirmatory testing could be
limited to one expert reference laboratory, or even to several
commercial laboratories, and in the past T. gondii tests at some
commercial laboratories have not been accurate.22
The diagnosis of toxoplasmosis can be difficult, especially
in immunosuppressed patients and in persons with congenital
disease. Diagnostic tools for toxoplasmosis, including poly-
merase chain reaction, more sensitive and specific IgM tests,
Western blots for comparison of maternal and infant antibody
response, and strain typing tests, would benefit from further
development.11,80–82
In addition, relatively little is known
regarding treatment efficacy for ocular disease.83,84
Improve-
ments in treatment could potentially be achieved through
1) trials to establish the efficacy for preventing congenital
transmission and sequlae in infants, as well as the optimal
medications and duration of therapy; and 2) collaboration
with those in the ophthalmologic community to improve detec-
tion and treatment of ocular disease and to create standard-
ized, evidence-based practices for ocular disease designed to
minimize morbidity and to prevent recurrent disease.
The reduction in prevalence of T. gondii infection in the
United States suggests that efforts to improve quality control
by meat producers and improved cat-care hygiene, as well
as efforts to increase knowledge about toxoplasmosis among
physicians and the public, have been successful in reducing
toxoplasmosis risk.30
Further reductions in infection could be
achieved through identification and mitigation of risk factors
for T. gondii infection, including 1) encouraging good produc-
tion practices by meat producers, 2) developing methods
to minimize environmental contamination of soil and water
with T. gondii, and 3) improving patient education and public
health messages to reduce ingestion of undercooked meat
and improve cat feces–related and soil-related hygiene.67,85,86
Further understanding of the impact of toxoplasmosis on
health, including mental health, is needed to help keep public
health resources focused on prevention efforts. Continued
evaluation of T. gondii infection using population-based stud-
ies to monitor the prevalence and temporal trends in infection
will be essential to measure the impact of prevention efforts
and guide adjustments in prevention strategies.
Received December 10, 2013. Accepted for publication January 31,
2014.
Disclaimer: The findings and conclusions in this report are those of
the authors and do not necessarily represent the official position of
the Centers for Disease Control and Prevention.
Authors’ addresses: Jeffrey L. Jones, Monica E. Parise, and Anthony E.
Fiore, Division of Parasitic Diseases and Malaria, Center for Global
Health, Centers for Disease Control and Prevention, Atlanta, GA,
E-mails: jlj1@cdc.gov, mep0@cdc.gov, and abf4@cdc.gov.
REFERENCES
1. Dubey JP, 2010. Toxoplasmosis of Animals and Humans. Second
edition. Boca Raton, FL: CRC Press.
2. Jones JL, Dubey JP, 2012. Foodborne toxoplasmosis. Clin Infect
Dis 55: 845–851.
3. Roghmann MC, Faulkner CT, Lefkowitz A, Patton S, Zimmerman
J, Morris JG Jr, 1999. Decreased seroprevalence for Toxo-
plasma gondii in Seventh Day Adventists in Maryland. Am J
Trop Med Hyg 60: 790–792.
4. Hill D, Coss C, Dubey JP, Wroblewski K, Sautter M, Hosten T,
Mun˜oz-Zanzi C, Mui E, Withers S, Boyer K, Hermes G, Coyne
J, Jagdis F, Burnett A, McLeod P, Morton H, Robinson D,
McLeod R, 2011. Identification of a sporozoite-specific antigen
from Toxoplasma gondii. J Parasitol 97: 328–337.
5. Boyer K, Hill D, Mui E, Wroblewski K, Karrison T, Dubey JP,
Sautter M, Noble AG, Withers S, Swisher C, Heydemann P,
Hosten T, Babiarz J, Lee D, Meier P, McLeod R; Toxo-
plasmosis Study Group, 2011. Unrecognized ingestion of
Toxoplasma gondii oocysts leads to congenital toxoplasmo-
sis and causes epidemics in North America. Clin Infect Dis
53: 1081–1089.
6. Su C, Khan A, Zhou P, Majumdar D, Ajzenberg D, Darde´ ML,
Zhu XQ, Ajioka JW, Rosenthal BM, Dubey JP, Sibley LD,
2012. Globally diverse Toxoplasma gondii isolates comprise
six major clades originating from a small number of distinct
ancestral lineages. Proc Natl Acad Sci USA 109: 5844–5849.
7. Lindsay DS, Dubey JP, 2011. Toxoplasma gondii: the chang-
ing paradigm of congenital toxoplasmosis. Parasitology 138:
1829–1831.
8. McLeod R, Boyer K, Lee D, Mui E, Wroblewski K, Karrison T,
Noble AG, Withers S, Swisher CN, Heydemann PT, Sautter
M, Babiarz J, Rabiah P, Meier P, Grigg ME; Toxoplasmosis
Study Group, 2012. Prematurity and severity are associated
with Toxoplasma gondii alleles (NCCCTS, 1981–2009). Clin
Infect Dis 54: 1595–1605.
9. Gilbert RE, Freeman K, Lago EG, Bahia-Oliveira LM, Tan HK,
Wallon M, Buffolano W, Stanford MR, Petersen E; European
Multicentre Study on Congenital Toxoplasmosis (EMSCOT),
2008. Ocular sequelae of congenital toxoplasmosis in Brazil
compared with Europe. PLoS Negl Trop Dis 2: e277.
NEGLECTED PARASITIC INFECTIONS: TOXOPLASMOSIS 797
5. 10. Shobab L, Pleyer U, Johnsen J, Metzner S, James ER, Torun N,
Fay MP, Liesenfeld O, Grigg ME, 2013. Toxoplasma sero-
type is associated with development of ocular toxoplasmosis.
J Infect Dis 208: 1520–1528.
11. Remington JS, McLeod R, Wilson CB, Desmonts G, Toxoplasmosis,
2011. Remington JS, Klein JO, Wilson CB, Nizet V, Maldonado
YA eds. Infectious Diseases of the Fetus and Newborn Infant.
Seventh edition. Philadelphia, PA: Elsevier Saunders, 918–1041.
12. Koppe JG, Loewer-Sieger DH, De Roever-Bonnet H, 1986.
Results of 20-year follow-up of congenital toxoplasmosis.
Am J Ophthalmol 101: 248–249.
13. Faucher B, Garcia-Meric P, Franck J, Minodier P, Francois P,
Gonnet S, L’Ollivier C, Piarroux R, 2012. Long-term ocular
outcome in congenital toxoplasmosis: a prospective cohort of
treated children. J Infect 64: 104–109.
14. Kodjikian L, Wallon M, Fleury J, Denis P, Binquet C, Peyron F,
Garweg JG, 2006. Ocular manifestations in congenital toxo-
plasmosis. Graefes Arch Clin Exp Ophthalmol 244: 14–21.
15. Peyron F, Garweg JG, Wallon M, Descloux E, Rolland M,
Barth J, 2011. Long-term impact of treated congenital toxo-
plasmosis on quality of life and visual performance. Pediatr
Infect Dis J 230: 597–600.
16. Torrey EF, Bartko JJ, Lun ZR, Yolken RH, 2007. Antibodies to
Toxoplasma gondii in patients with schizophrenia: a meta-
analysis. Schizophr Bull 33: 729–736.
17. Pearce BD, Kruszon-Moran D, Jones JL, 2012. The relationship
between Toxoplasma gondii infection and mood disorders in
the third national health and nutrition survey. Biol Psychiatry
72: 290–295.
18. Arling TA, Yolken RH, Lapidus M, Langenberg P, Dickerson
FB, Zimmerman SA, Balis T, Cabassa JA, Scrandis DA,
Tonelli LH, Postolache TT, 2009. Toxoplasma gondii antibody
titers and history of suicide attempts in patients with recurrent
mood disorders. J Nerv Ment Dis 197: 905–908.
19. Pedersen MG, Mortensen PB, Norgaard-Pedersen B, Postolache
TT, 2012. Toxoplasma gondii infection and self-directed vio-
lence in mothers. Arch Gen Psych 69: 1123–1130.
20. Gajewski PD, Falkenstein M, Hengstler JG, Golka K, 2014.
Toxoplasma gondii impairs memory in infected seniors. Brain
Behav Immun 36: 193–199.
21. Torrey EF, Yolken RH, 2013. Toxoplasma oocysts as a public
health problem. Trends Parasitol 29: 380–384.
22. Wilson M, Remington JS, Clavet C, Varney G, Press C, Ware D,
1997. Evaluation of six commercial kits for detection of human
immunoglobulin M antibodies to Toxoplasma gondii. The FDA
Toxoplasmosis Ad Hoc Working Group. J Clin Microbiol 35:
3112–3115.
23. Centers for Disease Control and Prevention, 2012. DPDx, Diag-
nostic Findings for Toxoplasmosis. Available at: http://www
.cdc.gov/dpdx/toxoplasmosis/dx.html. Accessed April 7, 2014.
24. Lappalainen M, Koskela P, Koskiniemi M, Amma¨la¨ P, Hiilesmaa
V, Teramo K, Raivio KO, Remington JS, Hedman K, 1993.
Toxoplasmosis acquired during pregnancy: improved sero-
diagnosis based on avidity of IgG. J Infect Dis 167: 691–697.
25. Robert-Gangneux F, Darde´ ML, 2012. Epidemiology of and
diagnostic strategies for toxoplasmosis. Clin Microbiol Rev
25: 264–296.
26. Montoya JG, Liesenfeld O, 2004. Toxoplasmosis. Lancet 363:
1965–1976.
27. Panel on Opportunistic Infections in HIV-Infected Adults and
Adolescents. Guidelines for the prevention and treatment of
opportunistic infections in HIV-infected adults and adolescents:
recommendations from the Centers for Disease Control and
Prevention, the National Institutes of Health, and the HIV
Medicine Association of the Infectious Diseases Society of
America. Available at: http://aidsinfo.nih.gov/contentfiles/
lvguidelines/adult_oi.pdf. Accessed April 2, 2014.
28. Montoya JG, Remington JS, 2008. Management of Toxoplasma
gondii infection during pregnancy. Clin Infect Dis 47: 554–566.
29. Jones JL, Kruzon-Moran D, Wilson M, McQuillan G, Navin T,
McAuley JB, 2001. Toxoplasma gondii in the United States,
seroprevalence and risk factors. Am J Epidemiol 154: 357–365.
30. Jones JL, Kruszon-Moran D, Sanders-Lewis K, Wilson M,
2007. Toxoplasma gondii infection in the United States, 1999–
2004, decline from the prior decade. Am J Trop Med Hyg 77:
405–410.
31. Jones JL, Kruszon-Moran D, Won K, Wilson M, Schantz PM,
2008. Toxoplasma gondii and Toxocara spp. co-infection. Am J
Trop Med Hyg 78: 35–39.
32. Scallan E, Hoekstra RM, Angulo FJ, Tauxe RV, Widdowson
MA, Roy SL, Jones JL, Griffin PM, 2011. Foodborne illness
acquired in the United States–major pathogens. Emerg Infect
Dis 17: 7–15.
33. Batz MB, Hoffmann S, Morris JG Jr, 2012. Ranking the disease
burden of 14 pathogens in food sources in the United States
using attribution data from outbreak investigations and expert
elicitation. J Food Prot 75: 1278–1291.
34. Jones JL, Holland GN, 2010. Annual burden of ocular toxoplas-
mosis in the United States. Am J Trop Med Hyg 82: 464–465.
35. Lum FL, Jones JL, Holland GN, Liesegang TJ, 2005. Survey of
ophthalmologists about ocular toxoplasmosis. Am J Ophthalmol
140: 724–726.
36. Jara M, Hsu HW, Eaton RB, Demaria A Jr, 2001. Epidemiology
of congenital toxoplasmosis identified by population-based
newborn screening in Massachusetts. Pediatr Infect Dis J 20:
1132–1135.
37. Neto EC, Rubin R, Schulte J, Giugliani R, 2004. Newborn
screening for congenital infectious diseases. Emerg Infect
Dis 10: 1068–1073.
38. Lopez A, Dietz VJ, Wilson M, Navin TR, Jones JL, 2000.
Preventing congenital toxoplasmosis. MMWR Recomm Rep
49: 57–75.
39. Dunn D, Wallon M, Peyron F, Petersen E, Peckham C, Gilbert R,
1999. Mother-to-child transmission of toxoplasmosis: risk esti-
mates for clinical counseling. Lancet 353: 1829–1833.
40. Guerina NG, Hsu HW, Meissner HC, Maguire JH, Lynfield R,
Stechenberg B, Abroms I, Pasternack MS, Hoff R, Eaton RB,
Grady GF; New England Regional Toxoplasma Working
Group, 1994. Neonatal serologic screening and early treatment
for congenital Toxoplasma gondii infection. N Engl J Med 330:
1858–1863.
41. Gilbert RE, Thalib L, Tan HK, Paul M, Wallon M, Petersen E;
European Multicentre Study on Congenital Toxoplasmosis,
2007. Screening for congenital toxoplasmosis: accuracy of
immunoglobulin M and immunoglobulin A tests after birth.
J Med Screen 14: 8–13.
42. Naessens A, Jenum PA, Pollak A, Decoster A, Lappalainen M,
Villena I, Lebech M, Stray-Pedersen B, Hayde M, Pinon JM,
Petersen E, Foulon W, 1999. Diagnosis of congenital toxo-
plasmosis in the neonatal period: a multicenter evaluation.
J Pediatr 135: 714–719.
43. Lebech M, Andersen O, Christensen NC, Hertel J, Nielsen HE,
Peitersen B, Rechnitzer C, Larsen SO, Nørgaard-Pedersen
B, Petersen E, 1999. Feasibility of neonatal screening for
Toxoplasma infection in the absence of prenatal treatment.
Danish Congenital Toxoplasmosis Study Group. Lancet 353:
1834–1837.
44. Kimball AC, Kean BH, Fucks F, 1971. Congenital toxoplasmosis:
a prospective study of 4,048 obstetric patients. Am J Obstet
Gynecol 111: 211–218.
45. Alford CA, Stagno S, Reynolds DW, 1974. Congenital toxoplas-
mosis: clinical, laboratory, and therapeutic considerations,
with special reference to subclinical disease. Bull N Y Acad
Med 50: 160–181.
46. Stillwaggon E, Carrier CS, Sautter M, McLeod R, 2011. Mater-
nal serologic screening to prevent congenital toxoplasmosis:
a decision-analytic economic model. PLoS Negl Trop Dis 5:
e1333.
47. Cornu C, Bissery A, Malbos C, Garwig R, Cocherel C, Ecochard
R, Peyron F, Wallon M, 2009. Factors affecting the adherence
to an antenatal screening programme: an experience with toxo-
plasmosis screening in France. Euro Surveill 14: 21–25.
48. Sagel U, Kremer A, Mikolajczyk RT, 2011. Incidence of mater-
nal Toxoplasma infection in pregnancy in Upper Austria,
2000–2007. BMC Infect Dis 11: 348.
49. Peyron F, Wallon M, Liou C, Garner P, 2000. Treatments for
toxoplasmosis in pregnancy. Cochrane Database Syst Rev
CD001684.
50. Peckham C, 2011. Screening for Toxoplasmosis. Expert Review
for United Kingdom Policy. Available at: http://www
.screening.nhs.uk/policydb_download.php?doc=138. Accessed
August 5, 2013.
798 JONES AND OTHERS
6. 51. UK National Screening Committee. Policy on Toxoplasmosis
Screening in Pregnancy (Updated December 2011). Available
at: http://www.screening.nhs.uk/toxoplasmosis. Accessed August
5, 2013.
52. Rudin C, Boubaker K, Raeber PA, Vaudaux B, Bucher HC,
Garweg JG, Hoesli I, Kind C, Hohlfeld P, 2008. Toxoplasmosis
during pregnancy and infancy, a new approach for Switzerland.
Swiss Med Wkly 138 (Suppl 168): 1–8.
53. Ro¨ser D, Nielsen HV, Petersen E, Saugmann-Jensen P,
Nørgaard-Pedersen PB, 2010. Congenital toxoplasmosis: a
report on the Danish neonatal screening programme 1999–2007.
J Inherit Metab Dis 33 (Suppl 2): S241–S247.
54. Paquet C, Yudin MH, 2013. Toxoplasmosis in pregnancy: preven-
tion, screening, and treatment. J Obstet Gynaecol Can 35: 78–79.
55. Miron D, Raz R, Luder A, 2002. Congenital toxoplasmosis in
Israel: to screen or not to screen. Isr Med Assoc J 4: 119–122.
56. American College of Obstetricians and Gynecologists, 2002.
ACOG practice bulletin. Perinatal viral and parasitic infec-
tions. Int J Gynaecol Obstet 76: 95–107.
57. Desmonts G, Couvreur J, 1974. Congenital toxoplasmosis. A pro-
spective study of 378 pregnancies. N Engl J Med 290: 1110–1116.
58. Thie´baut R, Leroy V, Alioum A, Binquet C, Poizat G, Salmi LR,
Gras L, Salamon R, Gilbert R, Cheˆne G, 2006. Biases in obser-
vational studies of the effect of prenatal treatment for congen-
ital toxoplasmosis. Eur J Obstet Gynecol Reprod Biol 124: 3–9.
59. Thie´baut R, Leproust S, Cheˆne G, Gilbert R; SYROCOT
(Systematic Review on Congenital Toxoplasmosis) Study
Group, 2007. Effectiveness of prenatal treatment for congen-
ital toxoplasmosis: a meta-analysis of individual patients’
data. Lancet 369: 115–122.
60. Gilbert R, Gras L; European Multicentre Study on Congenital
Toxoplasmosis, 2003. Effect of timing and type of treatment on
the risk of mother to child transmission of Toxoplasma
gondii. BJOG 110: 112–120.
61. Foulon W, Villena I, Stray-Pedersen B, Decoster A, Lappalainen
M, Pinon JM, Jenum PA, Hedman K, Naessens A, 1999. Treat-
ment of toxoplasmosis during pregnancy: a multicenter study
of impact on fetal transmission and children’s sequelae at age
1 year. Am J Obstet Gynecol 180: 410.
62. Gilbert RE, Gras L, Wallon M, Peyron F, Ades AE, Dunn DT,
2001. Effect of prenatal treatment on mother to child transmission
of Toxoplasma gondii: retrospective cohort study of 554 mother-
child pairs in Lyon, France. Int J Epidemiol 30: 1303–1308.
63. Gras L, Wallon M, Pollak A, Cortina-Borja M, Evengard B,
Hayde M, Petersen E, Gilbert R; European Multicenter Study
on Congenital Toxoplasmosis, 2005. Association between pre-
natal treatment and clinical manifestations of congenital toxo-
plasmosis in infancy: a cohort study in 13 European centres.
Acta Paediatr 94: 1721–1731.
64. Wallon M, Peyron F, Cornu C, Vinault S, Abrahamowicz M,
Bonithon Kopp C, Binquet C, 2013. Congenital Toxoplasma
infection: monthly prenatal screening diseases transmission
rate and improves clinical outcome at 3 years. Clin Infect Dis
56: 1223–1231.
65. Cortina-Borja M, Tan HK, Wallon M, Paul M, Prusa A,
Buffolano W, Malm G, Salt A, Freeman K, Petersen E, Gilbert
RE; European Multicentre Study on Congenital Toxoplasmo-
sis (EMSCOT), 2010. Prenatal treatment for serious neurolog-
ical sequelae of congenital toxoplasmosis: an observational
prospective cohort study. PLoS Med 7: e1000351.
66. Kieffer F, Wallon M, Garcia P, Thulliez P, Peyron F, Franck J,
2008. Risk factors for retinochoroiditis during the first 2 years
of life in infants with treated congenital toxoplasmosis. Pediatr
Infect Dis J 27: 27–32.
67. Jones JL, Ogunmodede F, Scheftel J, Kirkland E, Lopez A,
Schulkin J, Lynfield R, 2003. Toxoplasmosis-related knowl-
edge and practices among pregnant women in the United
States. Infect Dis Obstet Gynecol 11: 139–145.
68. Foulon W, Naessens A, Derde MP, 1994. Evaluation of the
possibilities for preventing congenital toxoplasmosis. Am J
Perinatol 11: 57–62.
69. Foulon W, Naessens A, Ho-Yen D, 2000. Prevention of congeni-
tal toxoplasmosis. J Perinat Med 28: 337–345.
70. Breugelmans M, Naessens A, Foulon W, 2004. Prevention of
toxoplasmosis during pregnancy: an epidemiologic survey over
22 consecutive years. J Perinat Med 32: 211–214.
71. Carter AO, Gelmon P, Wells GA, Toepell AP, 1989. The
effectiveness of a prenatal education programme for the pre-
vention of congenital toxoplasmosis. Epidemiol Infect 103:
539–545.
72. Pawlowski ZS, Gromadecka-Sutkiewicz M, Skommer J, Paul M,
Rokossowski H, Suchocka E, Schantz PM, 2001. Impact of
health education on knowledge and prevention behavior for
congenital toxoplasmosis; the experience in Poznan, Poland.
Health Educ Res 16: 493–502.
73. Gollub EL, Leroy V, Gilbert R, Cheˆne G, Wallon M; European
Toxoprevention Study Group (EUROTOXO), 2008. Effec-
tiveness of health education on Toxoplasma-related knowl-
edge, behavior, and risk of seroconversion in pregnancy. Eur
J Obstet Gynecol Reprod Biol 136: 137–145.
74. Di Mario S, Basevi V, Gagliotti C, Spettoli D, Gori G, D’Amico
R, Magrini N, 2013. Prenatal education for congenital toxo-
plasmosis. Cochrane Database Syst Rev CD006171.
75. Frenkel JK, Pfefferkorn ER, Smith DD, Fishback JL, 1991. Pro-
spective vaccine prepared from a new mutant of Toxoplasma
gondii for use in cats. Am J Vet Res 52: 759–763.
76. Buxton D, Innes EA, 1995. A commercial vaccine for ovine
toxoplasmosis. Parasitology 110: S11–S16.
77. Bader TJ, Macones GA, Asch DA, 1997. Prenatal Screening for
toxoplasmosis. Obstet Gynecol 90: 457–464.
78. Mittendorf R, Pryde P, Herschel M, Williams MA, 1999.
Is routine antenatal toxoplasmosis screening justified in
the United States? Statistical considerations in the appli-
cation of medical screening tests. Clin Obstet Gynecol 42:
163–173.
79. Khoshnood B, De Vigan C, Goffinet F, Leroy V, 2007. Prenatal
screening and diagnosis of congenital toxoplasmosis: a review
of safety issues and psychological consequences for women
who undergo screening. Prenat Diagn 27: 395–403.
80. Remington JS, Thulliez P, Montoya JG, 2004. Recent develop-
ments for diagnosis of toxoplasmosis. J Clin Microbiol 42:
941–945.
81. Petersen E, 2007. Toxoplasmosis. Semin Fetal Neonatal Med 12:
214–223.
82. McAuley JB, Jones JL, Singh AK, 2011. Toxoplasma. Versalovic
J, Carroll KC, Funke G, Jorgensen JH, Landry ML, Warnock
DW eds. Manual of Clinical Microbiology. Tenth edition.
Washington, DC: American Society for Microbiology Press,
2217–2238.
83. Holland GN, 2004. Ocular toxoplasmosis: a global reassess-
ment. Part II: disease manifestations and management. Am J
Ophthalmol 137: 1–17.
84. de-la-Torre A, Stanford M, Curi A, Jaffe GJ, Gomez-Marin JE,
2011. Therapy for ocular toxoplasmosis. Ocul Immunol Inflamm
19: 314–320.
85. Jones JL, Krueger A, Schulkin J, Schantz PM, 2010. Toxoplasmo-
sis prevention and testing in pregnancy, survey of obstetrician-
gynaecologists. Zoonoses Public Health 57: 27–33.
86. Jones JL, Schulkin J, Maguire JH, 2005. Therapy for common
parasitic diseases in pregnancy in the United States: a review
and a survey of obstetrician/gynecologists’ level of knowledge
about these diseases. Obstet Gynecol Surv 60: 386–393.
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